Design, Synthesis and Biological Evaluation of Substituted Guanidine Indole Derivatives as Potential Inhibitors of HIV-1 Tat-TAR Interaction

Title:Design, Synthesis and Biological Evaluation of Substituted Guanidine Indole Derivatives as Potential Inhibitors of HIV-1 Tat-TAR Interaction

Volume: 10 Issue: 7

Author(s): Jun Wang, Yan Wang, Zhenyu Li, Peng Zhan, Rujun Bai, Christophe Pannecouque, Jan Balzarini, Erik De Clercq and Xinyong Liu

Affiliation:

Keywords: Drug design, guanidine indole synthesis, HIV-1 Tat, HIV-1 TAR, inhibitors.

Abstract: The interaction between the HIV-1 transactivator protein Tat and RNA response element (TAR) plays a critical role in HIV-1 transcription. Based on the pharmacophore model of reported inhibitors, a series of novel substituted guanidine indole derivatives was designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 inhibitory activity using the III_B strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity against HIV-1 III_B. Quite unexpectedly, compound a-7 was also endowed with the moderate anti-HIV-2 potency (EC₅₀ = 58.14 µM). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.

Cite this article as:

Wang Jun, Wang Yan, Li Zhenyu, Zhan Peng, Bai Rujun, Pannecouque Christophe, Balzarini Jan, Clercq De Erik and Liu Xinyong, Design, Synthesis and Biological Evaluation of Substituted Guanidine Indole Derivatives as Potential Inhibitors of HIV-1 Tat-TAR Interaction, Medicinal Chemistry 2014; 10 (7) . https://dx.doi.org/10.2174/1573406410666140306151815